Next Generation cancer 'omics technologies are revolutionizing our understanding of cancer, but our approaches to clinical investigation have not kept pace. The Cancer Genome Atlas (TCGA) is delivering an impressive body of data and technical advances in data analysis, but is analytically limited by the uncontrolled clinical settings in which the samples were accrued. We therefore propose to match the technical expertise of The Genome Institute at Washington University with the accrual power and clinical expertise of the NRG cooperative group to provide clinical and biological annotation for the vast quantities of new data generated by high-throughput sequencing platforms. We also anticipate major technical advances in the proteomics field as a result of the investment by the NCI in the Clinical Proteomics Tumor Analysis Consortium (CPTAC). We therefore propose the Integrated Translational Genoproteomlcs Center (ITGC) that will nucleate a concerted effort to integrate DNA, RNA and Peptide sequencing into NRG clinical trials to a) increase our biological understanding of common epithelial cancers, b) develop biomarkers of treatment response and c) identify new therapeutic targets. This proposal includes plans for five proteogenomic pilot projects with NRG Oncology In breast cancer, head and neck cancer, ovarian cancer, rectal cancer and prostate cancer. The aims of these demonstration projects are to fully integrate proteogenomics into prospective clinical trials of preoperative systemic therapy, to develop genoproteomic assays for clinical trial eligibility and stratification and to integrate mass-spectrometry-based and reverse phase protein array-based (RPPA) proteomics into the existing genomic sample analysis pipeline. Our strategic objective is to bring comprehensive discovery science into the cooperative group setting. This will drive the NRG Oncology organ site committees to more deeply appreciate the fundamental biology that underlies the diseases that they treat and should ultimately raise the quality of the clinical trial hypotheses that are pursue.